Early-life injuries and the development of attention-deficit/hyperactivity disorder

Wimberley, Theresa, Brikell, Isabell, Pedersen, Emil M., Agerbo, Esben, Vilhjálmsson, Bjarni J., Albiñana, Clara, Privé, Florian, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X, Langley, Kate ORCID: https://orcid.org/0000-0002-2033-2657, Riglin, Lucy, Simonsen, Marianne, Nielsen, Helena S., Børglum, Anders D., Nordentoft, Merete, Mortensen, Preben B. and Dalsgaard, Søren 2022. Early-life injuries and the development of attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry 83 (1) 10.4088/JCP.21m14033

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Abstract

Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Item Type:	Article
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Physicians Postgraduate Press
ISSN:	1555-2101
Date of First Compliant Deposit:	7 January 2022
Date of Acceptance:	23 August 2021
Last Modified:	29 Nov 2022 10:29
URI:	https://orca.cardiff.ac.uk/id/eprint/146460

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